One of the ultimate goals of wound healing research is to find effective healing techniques that utilize the regeneration of similar tissues. This involves the modification of various wound dressing biomaterials for proper wound management. The biopolymer chitosan (beta-1,4-D-glucosamine) has natural biocompatibility and biodegradability that render it suitable for wound management. By definition, a biocompatible biomaterial does not have toxic or injurious effects on biological systems. Chemical and physical modifications of chitosan influence its biocompatibility and biodegradability to an uncertain degree. Hence, the modified biomedical-grade of chitosan derivatives should be pre-examined in vitro in order to produce high-quality, biocompatible dressings. In vitro toxicity examinations are more favorable than those performed in vivo, as the results are more reproducible and predictive. In this paper, basic in vitro tools were used to evaluate cellular and molecular responses with regard to the biocompatibility of biomedical-grade chitosan. Three paramount experimental parameters of biocompatibility in vitro namely cytocompatibility, genotoxicity and skin pro-inflammatory cytokine expression, were generally reviewed for biomedical-grade chitosan as wound dressing.
Arabinoxylan (AX) is a natural biological macromolecule with several potential biomedical applications. In this research, AX, nano-hydroxyapatite (n-HAp) and titanium dioxide (TiO2) based polymeric nanocomposite scaffolds were fabricated by the freeze-drying method. The physicochemical characterizations of these polymeric nanocomposite scaffolds were performed for surface morphology, porosity, swelling, biodegradability, mechanical, and biological properties. The scaffolds exhibited good porosity and rough surface morphology, which were efficiently controlled by TiO2 concentrations. MC3T3-E1 cells were employed to conduct the biocompatibility of these scaffolds. Scaffolds showed unique biocompatibility in vitro and was favorable for cell attachment and growth. PNS3 proved more biocompatible, showed interconnected porosity and substantial mechanical strength compared to PNS1, PNS2 and PNS4. Furthermore, it has also showed more affinity to cells and cell growth. The results illustrated that the bioactive nanocomposite scaffold has the potential to find applications in the tissue engineering field.
Globally, people suffering from bone disorders are steadily increasing and bone tissue engineering is an advanced approach to treating fractured and defected bone tissues. In this study, we have prepared polymeric nanocomposite by free-radical polymerization from sodium alginate, hydroxyapatite, and silica with different GO amounts. The porous scaffolds were fabricated using the freeze drying technique. The structural, morphological, mechanical, and wetting investigation was conducted by Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscope, universal tensile machine, and water contact angle characterization techniques. The swelling, biodegradation, and water retention were also studied. The biological studies were performed (cell viability, cell adherence, proliferation, and mineralization) against osteoblast cell lines. Scaffolds have exhibited different pore morphology SAG-1 (pore size = 414.61 ± 56 μm and porosity = 81.45 ± 2.17 %) and SAG-4 (pore size = 195.97 ± 82 μm and porosity = 53.82 ± 2.45 %). They have different mechanical behavior as SAG-1 has the least compression strength and compression modulus 2.14 ± 2.35 and 16.51 ± 1.27 MPa. However, SAG-4 has maximum compression strength and compression modulus 13.67 ± 2.63 and 96.16 ± 1.97 MPa with wetting behavior 80.70° and 58.70°, respectively. Similarly, SAG-1 exhibited the least and SAG-4 presented maximum apatite mineral formation, cell adherence, cell viability, and cell proliferation against mouse pre-osteoblast cell lines. The increased GO amount provides different multifunctional materials with different characteristics. Hence, the fabricated scaffolds could be potential scaffold materials to treat and regenerate fracture bone tissues in bone tissue engineering.
Carbohydrate polymers are biological macromolecules that have sparked a lot of interest in wound healing due to their outstanding antibacterial properties and sustained drug release. Arabinoxylan (ARX), Chitosan (CS), and reduced graphene oxide (rGO) sheets were combined and crosslinked using tetraethyl orthosilicate (TEOS) as a crosslinker to fabricate composite hydrogels and assess their potential in wound dressing for skin wound healing. Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and biological assays were used to evaluate the composite hydrogels. FTIR validated the effective fabrication of the composite hydrogels. The rough morphologies of the composite hydrogels were revealed by SEM and AFM (as evident from the Ra values). ATC-4 was discovered to have the roughest surface. TEM revealed strong homogeneous anchoring of the rGO to the polymer matrix. However, with higher amount of rGO agglomeration was detected. The % swelling at various pHs (1-13) revealed that the hydrogels were pH-sensitive. The controlled release profile for the antibacterial drug (Silver sulfadiazine) evaluated at various pH values (4.5, 6.8, and 7.4) in PBS solution and 37 °C using the Franz diffusion method revealed maximal drug release at pH 7.4 and 37 °C. The antibacterial efficacy of the composite hydrogels against pathogens that cause serious skin diseases varied. The MC3T3-E1 cell adhered, proliferated, and differentiated well on the composite hydrogels. MC3T3-E1 cell also illustrated excellent viability (91%) and proper cylindrical morphologies on the composite hydrogels. Hence, the composite hydrogels based on ARX, CS, and rGO are promising biomaterials for treating and caring for skin wounds.
Bioceramic nanoparticles with high specific surface area often tend to agglomerate in the polymer matrix, which results in undesirable mechanical properties of the composites and poor cell spreading and attachment. In the present work, bredigite (BR) nanoparticles were modified with an organosilane coupling agent, 3-glycidoxypropyltrimethoxysilane (GPTMS), to enhance its dispersibility in the polymer matrix. The polyhydroxybutyrate-co-hydroxyvaletare (PHBV) nanofibrous scaffolds containing either bredigite or GPTMS-modified bredigite (G-BR) nanoparticles were fabricated using electrospinning technique and characterized using scanning electron microscopy, transmission electron microscopy, and tensile strength. Results demonstrated that modification of bredigite was effective in enhancing nanoparticle dispersion in the PHBV matrix. PHBV/G-BR scaffold showed improved mechanical properties compared to PHBV and PHBV/BR, especially at the higher concentration of nanoparticles. In vitro bioactivity assay performed in the simulated body fluid (SBF) indicated that composite PHBV scaffolds were able to induce the formation of apatite deposits after incubation in SBF. From the results of in vitro biological assay, it is concluded that the synergetic effect of BR and GPTMS provided an enhanced hFob cells attachment and proliferation. The developed PHBV/G-BR nanofibrous scaffolds may be considered for application in bone tissue engineering.
To compare the effect of bovine bone derived porous hydroxyapatite (BDHA) scaffold on proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hMSCs) compared with commercial hydroxyapatite (CHA) scaffold.
Natural biopolymers have many attractive medical applications; however, complications due to fibrosis caused a reduction in diffusion and dispersal of nutrients and waste products. Consequently, severe immunocompatibility problems and poor mechanical and degradation properties in synthetic polymers ensue. Hence, the present study investigates a novel hydrogel material synthesized from caprolactone, ethylene glycol, ethylenediamine, polyethylene glycol, ammonium persulfate, and tetramethylethylenediamine via chemo-enzymatic route. Spectroscopic analyses indicated the formation of polyurea and polyhydroxyurethane as the primary building block of the hydrogel starting material. Biocompatibility studies showed positive observation in biosafety test using direct contact cytotoxicity assay in addition to active cellular growth on the hydrogel scaffold based on fluorescence observation. The synthesized hydrogel also exhibited (self)fluorescence properties under specific wavelength excitation. Hence, synthesized hydrogel could be a potential candidate for medical imaging as well as tissue engineering applications as a tissue expander, coating material, biosensor, and drug delivery system.
In this study, a chitosan co-polymer scaffold was prepared by mixing poly(vinyl alcohol) (PVA), NO, carboxymethyl chitosan (NOCC) and polyethylene glycol (PEG) solutions to obtain desirable properties for chondrocyte cultivation. Electron beam (e-beam) radiation was used to physically cross-link these polymers at different doses (30 kGy and 50 kGy). The co-polymers were then lyophilized to form macroporous three-dimensional (3-D) matrix. Scaffold morphology, porosity, swelling properties, biocompatibility, expression of glycosaminoglycan (GAG) and type II collagen following the seeding of primary chondrocytes were studied up to 28 days. The results demonstrate that irradiation of e-beam at 50 kGy increased scaffold porosity and pore sizes subsequently enhanced cell attachment and proliferation. Scanning electron microscopy and transmission electron microscopy revealed extensive interconnected microstructure of PVA-PEG-NOCC, demonstrated cellular activities on the scaffolds and their ability to maintain chondrocyte phenotype. In addition, the produced PVA-PEG-NOCC scaffolds showed superior swelling properties, and increased GAG and type II collagen secreted by the seeded chondrocytes. In conclusion, the results suggest that by adding NOCC and irradiation cross-linking at 50 kGy, the physical and biological properties of PVA-PEG blend can be further enhanced thereby making PVA-PEG-NOCC a potential scaffold for chondrocytes.
A poly(vinyl alcohol) (PVA) hydrogel composite scaffold containing N,O-carboxymethylated chitosan (NOCC) was tested to assess its potential as a scaffold for cartilage tissue engineering in a weight-bearing environment. The mechanical properties under unconfined compression for different hydration periods were investigated. The effect of supplementing PVA with NOCC (20wt.% PVA:5vol.% NOCC) produced a porosity of 43.3% and this was compared against a non-porous PVA hydrogel (20g PVA: 100ml of water, control). Under non-hydrated conditions, the porous PVA-NOCC hydrogel behaved in a similar way to the control non-porous PVA hydrogel, with similar non-linear stress-strain response under unconfined compression (0-30% strain). After 7days' hydration, the porous hydrogel demonstrated a reduced stiffness (0.002kPa, at 25% strain), resulting in a more linear stiffness relationship over a range of 0-30% strain. Poisson's ratio for the hydrated non-porous and porous hydrogels ranged between 0.73 and 1.18, and 0.76 and 1.33, respectively, suggesting a greater fluid flow when loaded. The stress relaxation function for the porous hydrogel was affected by the hydration period (from 0 to 600s); however the percentage stress relaxation regained by about 95%, after 1200s for all hydration periods assessed. No significant differences were found between the different hydration periods between the porous hydrogels and control. The calculated aggregate modulus, H(A), for the porous hydrogel reduced drastically from 10.99kPa in its non-hydrated state to about 0.001kPa after 7days' hydration, with the calculated shear modulus reducing from 30.92 to 0.14kPa, respectively. The porous PVA-NOCC hydrogel conformed to a biphasic, viscoelastic model, which has the desired properties required for any scaffold in cartilage tissue engineering.
Standard prosthodontic procedures require five visits to construct a set of complete maxillary and mandibular dentures. Various attempts have been made to reduce these procedures to four or three appointments. However, most of these techniques require the use of visible light polymerized resin as the final denture base materials. Visible light-cured resin materials have inferior physical properties and biocompatibility problems as compared with heat cured polymethylmethacrylate. This paper describes a system of complete denture construction which requires three clinical appointments instead of the usual five visits. This system is made possible by using the VLC base/tray material as the preliminary impression material as well as the application of a new biometric wax occlusion rim. It retains the use of polymethylmethacrylate as the denture base material. This system also utilizes all the procedures used in the conventional five appointment system of complete denture construction.
A major weakness of current orthopedic implant materials, for instance sintered hydroxyapatite (HA), is that they exist as a hardened form, requiring the surgeon to fit the surgical site around an implant to the desired shape. This can cause an increase in bone loss, trauma to the surrounding tissue, and longer surgical time. A convenient alternative to harden bone filling materials are injectable bone substitutes (IBS). In this article, recent progress in the development and application of calcium phosphate (CP)-based composites use as IBS is reviewed. CP materials have been used widely for bone replacement because of their similarity to the mineral component of bone. The main limitation of bulk CP materials is their brittle nature and poor mechanical properties. There is significant effort to reinforce or improve the mechanical properties and injectability of calcium phosphate cement (CPC) and this review resumes different alternatives presented in this specialized literature.
Superparamagnetic iron oxide nanoparticles (MNPs) with appropriate surface chemistry exhibit many interesting properties that can be exploited in a variety of biomedical applications such as magnetic resonance imaging contrast enhancement, tissue repair, hyperthermia, drug delivery and in cell separation. These applications required that the MNPs such as iron oxide Fe₃O₄ magnetic nanoparticles (Fe₃O₄ MNPs) having high magnetization values and particle size smaller than 100 nm. This paper reports the experimental detail for preparation of monodisperse oleic acid (OA)-coated Fe₃O₄ MNPs by chemical co-precipitation method to determine the optimum pH, initial temperature and stirring speed in order to obtain the MNPs with small particle size and size distribution that is needed for biomedical applications. The obtained nanoparticles were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray fluorescence spectrometry (EDXRF), thermogravimetric analysis (TGA), X-ray powder diffraction (XRD), and vibrating sample magnetometer (VSM). The results show that the particle size as well as the magnetization of the MNPs was very much dependent on pH, initial temperature of Fe²⁺ and Fe³⁺ solutions and steering speed. The monodisperse Fe₃O₄ MNPs coated with oleic acid with size of 7.8 ± 1.9 nm were successfully prepared at optimum pH 11, initial temperature of 45°C and at stirring rate of 800 rpm. FTIR and XRD data reveal that the oleic acid molecules were adsorbed on the magnetic nanoparticles by chemisorption. Analyses of TEM show the oleic acid provided the Fe₃O₄ particles with better dispersibility. The synthesized Fe₃O₄ nanoparticles exhibited superparamagnetic behavior and the saturation magnetization of the Fe₃O₄ nanoparticles increased with the particle size.
The actual in vivo tissue scaffold offers a three-dimensional (3D) structural support along with a nano-textured surfaces consist of a fibrous network in order to deliver cell adhesion and signaling. A scaffold is required, until the tissue is entirely regenerated or restored, to act as a temporary ingrowth template for cell proliferation and extracellular matrix (ECM) deposition. This review depicts some of the most significant three dimensional structure materials used as scaffolds in various tissue engineering application fields currently being employed to mimic in vivo features. Accordingly, some of the researchers' attempts have envisioned utilizing graphene for the fabrication of porous and flexible 3D scaffolds. The main focus of this paper is to evaluate the topographical and topological optimization of scaffolds for tissue engineering applications in order to improve scaffolds' mechanical performances.
The current study is proposing a design envelope for porous Ti-6Al-4V alloy femoral stems to survive under fatigue loads. Numerical computational analysis of these stems with a body-centered-cube (BCC) structure is conducted in ABAQUS. Femoral stems without shell and with various outer dense shell thicknesses (0.5, 1.0, 1.5, and 2 mm) and inner cores (porosities of 90, 77, 63, 47, 30, and 18%) are analyzed. A design space (envelope) is derived by using stem stiffnesses close to that of the femur bone, maximum fatigue stresses of 0.3σys in the porous part, and endurance limits of the dense part of the stems. The Soderberg approach is successfully employed to compute the factor of safety Nf > 1.1. Fully porous stems without dense shells are concluded to fail under fatigue load. It is thus safe to use the porous stems with a shell thickness of 1.5 and 2 mm for all porosities (18-90%), 1 mm shell with 18 and 30% porosities, and 0.5 mm shell with 18% porosity. The reduction in stress shielding was achieved by 28%. Porous stems incorporated BCC structures with dense shells and beads were successfully printed.
Calcium silicate (CaSiO3, CS) ceramic composites reinforced with graphene nanoplatelets (GNP) were prepared using hot isostatic pressing (HIP) at 1150°C. Quantitative microstructural analysis suggests that GNP play a role in grain size and is responsible for the improved densification. Raman spectroscopy and scanning electron microscopy showed that GNP survived the harsh processing conditions of the selected HIP processing parameters. The uniform distribution of 1 wt.% GNP in the CS matrix, high densification and fine CS grain size help to improve the fracture toughness by ∼130%, hardness by ∼30% and brittleness index by ∼40% as compared to the CS matrix without GNP. The toughening mechanisms, such as crack bridging, pull-out, branching and deflection induced by GNP are observed and discussed. The GNP/CS composites exhibit good apatite-forming ability in the simulated body fluid (SBF). Our results indicate that the addition of GNP decreased pH value in SBF. Effect of addition of GNP on early adhesion and proliferation of human osteoblast cells (hFOB) was measured in vitro. The GNP/CS composites showed good biocompatibility and promoted cell viability and cell proliferation. The results indicated that the cell viability and proliferation are affected by time and concentration of GNP in the CS matrix.
Calcium silicate (CaSiO3, CS) ceramics are promising bioactive materials for bone tissue engineering, particularly for bone repair. However, the low toughness of CS limits its application in load-bearing conditions. Recent findings indicating the promising biocompatibility of graphene imply that graphene can be used as an additive to improve the mechanical properties of composites. Here, we report a simple method for the synthesis of calcium silicate/reduced graphene oxide (CS/rGO) composites using a hydrothermal approach followed by hot isostatic pressing (HIP). Adding rGO to pure CS increased the hardness of the material by ∼40%, the elastic modulus by ∼52%, and the fracture toughness by ∼123%. Different toughening mechanisms were observed including crack bridging, crack branching, crack deflection, and rGO pull-out, thus increasing the resistance to crack propagation and leading to a considerable improvement in the fracture toughness of the composites. The formation of bone-like apatite on a range of CS/rGO composites with rGO weight percentages ranging from 0 to 1.5 has been investigated in simulated body fluid (SBF). The presence of a bone-like apatite layer on the composite surface after soaking in SBF was demonstrated by X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM). The biocompatibility of the CS/rGO composites was characterized using methyl thiazole tetrazolium (MTT) assays in vitro. The cell adhesion results showed that human osteoblast cells (hFOB) can adhere to and develop on the CS/rGO composites. In addition, the proliferation rate and alkaline phosphatase (ALP) activity of cells on the CS/rGO composites were improved compared with the pure CS ceramics. These results suggest that calcium silicate/reduced graphene oxide composites are promising materials for biomedical applications.
Functionally graded material (FGM) is a heterogeneous composite material including a number of constituents that exhibit a compositional gradient from one surface of the material to the other subsequently, resulting in a material with continuously varying properties in the thickness direction. FGMs are gaining attention for biomedical applications, especially for implants, owing to their reported superior composition. Dental implants can be functionally graded to create an optimized mechanical behavior and achieve the intended biocompatibility and osseointegration improvement. This review presents a comprehensive summary of biomaterials and manufacturing techniques researchers employ throughout the world. Generally, FGM and FGM porous biomaterials are more difficult to fabricate than uniform or homogenous biomaterials. Therefore, our discussion is intended to give the readers about successful and obstacles fabrication of FGM and porous FGM in dental implants that will bring state-of-the-art technology to the bedside and develop quality of life and present standards of care.
Stimuli responsive hydrogels have shown enormous potential as a carrier for targeted drug delivery. In this study we have developed novel pH responsive hydrogels for the delivery of 5-fluorouracil (5-FU) in order to alleviate its antitumor activity while reducing its toxicity. We used 2-(methacryloyloxyethyl) trimetylammonium chloride a positively charged monomer and methacrylic acid for fabricating the pH responsive hydrogels. The released 5-FU from all except hydrogel (GEL-5) remained biologically active against human colon cancer cell lines [HT29 (IC50 = 110-190 μg ml(-1)) and HCT116 (IC50 = 210-390 μg ml(-1))] but not human skin fibroblast cells [BJ (CRL2522); IC50 ≥ 1000 μg ml(-1)]. This implies that the copolymer hydrogels (1-4) were able to release 5-FU effectively to colon cancer cells but not normal human skin fibroblast cells. This is probably due to the shorter doubling time that results in reduced pH in colon cancer cells when compared to fibroblast cells. These pH sensitive hydrogels showed well defined cell apoptosis in HCT116 cells through series of events such as chromatin condensation, membrane blebbing, and formation of apoptotic bodies. No cell killing was observed in the case of blank hydrogels. The results showed the potential of these stimuli responsive polymer hydrogels as a carrier for colon cancer delivery.
Titanium and its alloy are known as important load-bearing biomaterials. The major drawbacks of these metals are fibrous formation and low corrosion rate after implantation. The surface modification of biomedical implants through various methods such as plasma spray improves their osseointegration and clinical lifetime. Different materials have been already used as coatings on biomedical implant, including calcium phosphates and bioglass. However, these materials have been reported to have limited clinical success. The excellent bioactivity of calcium silicate (Ca-Si) has been also regarded as coating material. However, their high degradation rate and low mechanical strength limit their further coating application. Trace element modification of (Ca-Si) bioceramics is a promising method, which improves their mechanical strength and chemical stability. In this review, the potential of trace element-modified silicate coatings on better bone formation of titanium implant is investigated.
Wounds with full-thickness skin loss are commonly managed by skin grafting. In the absence of a graft, reepithelialization is imperfect and leads to increased scar formation. Biomaterials can alter wound healing so that it produces more regenerative tissue and fewer scars. This current study use the new chitosan based biomaterial in full-thickness wound with impaired healing on rat model. Wounds were evaluated after being treated with a chitosan dermal substitute, a chitosan skin substitute, or duoderm CGF. Wounds treated with the chitosan skin substitute showed the most re-epithelialization (33.2 ± 2.8%), longest epithelial tongue (1.62 ± 0.13 mm), and shortest migratory tongue distance (7.11 ± 0.25 mm). The scar size of wounds treated with the chitosan dermal substitute (0.13 ± 0.02 cm) and chitosan skin substitute (0.16 ± 0.05 cm) were significantly decreased (P < 0.05) compared with duoderm (0.45 ± 0.11 cm). Human leukocyte antigen (HLA) expression on days 7, 14, and 21 revealed the presence of human hair follicle stem cells and fibroblasts that were incorporated into and surviving in the irradiated wound. We have proven that a chitosan dermal substitute and chitosan skin substitute are suitable for wound healing in full-thickness wounds that are impaired due to radiation.